Norlabdane oxide may be structurally shown as follows: ##STR1## Compound (1) is presently one of the most commercially important perfume components for providing ambergris-type odors. Ambergris is a metabolic product of sperm whales which has been used in the past as a valuable constituent of fine fragrances..sup.1 Natural ambergris itself is no longer used for this purpose. However, there is a demand for perfume ingredients with ambergris-type odors. Compound (1) represents one of the preferred synthetic compounds with desirable ambergris-type odor and is commercially available under various names (notably as Amberlyn, Ambroxan, Ambrox or Amberoxide)..sup.2
Since the first reported synthesis of compound (1),.sup.3 a number of synthesis procedures have been proposed. However, these are complex and laborious procedures which provide only a low yield of the desired product. Typically, these procedures include synthesis from sesqui- and diterpenoids..sup.4 More recently, it has been shown that naturally occurring (-)-sclareol.sup.5,6 or communic acid.sup.7,8 can be used as starting materials to prepare (1).
The reported procedures in going from the naturally occurring sclareol of structure (2): ##STR2## to the desired compound (1).sup.5,6, are, generally speaking, preferable to the communic acid pathways because the overall yields seem to be higher using (2), apparently due to a decrease in the number of steps required. In any case, all of the previously known methods using sclareol (2), as well as the current industrial process,.sup.1 lead to the formation of the diol (3): ##STR3## This must then be cyclized to give compound (1). This requires considerable care as the less desired, more thermodynamically stable iso-form of compound (1) may result.sup.9,10. This iso-form possesses inferior olfactive properties and serves to reduce the overall effectiveness of the synthesis process with respect to the production of compound (1).
In the above-mentioned application Ser. No. 08/279,160, we have described an improved process for preparing compound (1) starting with (-)-sclareol. The process involves a three-stage synthesis of compound (1) starting with sclareol (2) which avoids the cyclization step referred to above. The process comprises a reaction sequence wherein sclareol (2) is subjected to osmium tetroxide OsO.sub.4, oxidation or catalyzed rearrangement to form methyl-ketone intermediates (4a) and (4b) after which intermediates 4(a) and 4(b) are converted by Baeyer-Villiger oxidation to give the acetates (5a) and (5b) which are both then converted e.g. by reduction in the presence of a Lewis acid to the desired compound (1). An advantage of the process is that epimeric mixtures of (4a) and (4b), hereinafter referred to for convenience as methyl ketone (4), may be used without separation since the products (5a) and (5b) obtained therefrom both give the desired compound (1) on reduction. ##STR4##
An important step in the process of Ser. No. 08/279,160 involves the osmium tetroxide/sodium periodate oxidation cleavage of (-)-sclareol followed by an osmium catalyzed rearrangement affording the methyl ketone (4) in excellent yield. As noted above, Baeyer-Villigar oxidation of the methyl ketone followed by reduction with a variety of reducing agents in the presence of a Lewis acid completes the synthesis of (-)-norlabdane oxide.
While the process of U.S. application Ser. No. 08/279,160 represents an important improvement over previously available procedures for making norlabdane oxide, it would be desirable, if possible, to avoid the use of osmium tetroxide which is expensive and toxic. Accordingly, the principal object of the present invention is to modify the process of U.S. Ser. No. 08/279,160 whereby the use of osmium tetroxide may be avoided while otherwise maintaining the advantages of the process described in Ser. No. 08/279,160. A more specific object of the invention is to provide an improved process for preparing the key methyl ketone intermediate (4) from sclareol whereby the ultimately desired flavoring product can be obtained more readily in outstanding yield.